The properties of angiotensin II (AII) receptors and their intracellular signalling pathways were studied in the adrenal glomerulosa cell and other target tissues. Purification of photolabeled AII receptors of the bovine adrenal gland was performed by detergent solubilization and fractionation by ion exchange, lectin-affinity, ligand-affinity, and immunoaffinity chromatography. The steroidogenic action of AII depends upon mobilization of intracellular calcium by the products of polyphosphoinositide turnover, and also on calcium entry through voltage-sensitive channels. A new method for the analysis of hormone receptors coupled to calcium mobilization was developed by the use of (3H)inositol-labeled Xenopus oocytes, in which AII receptors expressed from adrenal and pituitary mRNA were shown to be coupled to phosphoinositide hydrolysis. In conjunction with procedures being developed to measure receptor concentration and calcium mobilization in individual oocytes, this method will be applied to the screening of mRNA from cDNA expression libraries to isolate functional cDNA encoding receptors for calcium-mobilizing hormones including AII, vasopressin and GnRH. Direct evidence for coupling of the AII receptor to phospholipase C by a guanine nucleotide regulatory protein was obtained in permeabilized adrenal cells, in which InsP3 production was stimulated by guanine nucleotides and fluoride, as well as by AII. In adrenal glomerulosa cells, the conversion of Ins-1,4,5-P3 to Ins-1,3,4,5- P4 was shown to be catalyzed by a calcium-calmodulin dependent 3- kinase, and the identity of the new lnsP4 formed from Ins-1,3,4-P3 was determined chemically to be Ins-1,3,4,6-P4. A further inositol tetrakisphosphate was identified in AII-stimulated cells and bears a precursor-product relationship with InsP5. The effects of lithium on inositol phosphate metabolism were shown to include inhibition of inositol-1,3,4-P3 breakdown to Ins-3,4-P2 as well as of Ins-4-P to inositol, and also marked attenuation of Ins-1,4,5- P3 production during prolonged incubation due to inhibition of phospholipase C-catalyzed breakdown of plasma-membrane polyphosphoinositides. The intracellular receptors which mediate the calcium-mobilizing action of InsP3 were found to co-purify with InsP3-sensitive calcium releasing vesicles in the hepatic plasma membrane fraction, suggesting the existence of membrane associated organelles from which InsP3 promotes calcium release into the cytoplasm during peptide hormone action.